Coronary heart disease is the single leading cause of death in America today (American Heart Association's “1999 Heart and Stroke Statistical Update”). This disease, as with various other cardiovascular disorders, is characterized by the narrowing of arteries and inadequate blood flow to critical tissues.
Currently used clinical methods for improving blood flow in a diseased or otherwise damaged heart involve invasive surgical techniques such as coronary by-pass surgery, angioplasty, and endarterectomy. Such procedures naturally involve high-degrees of inherent risk during and after surgery, and often only provide a temporary remedy to cardiac ischemia.
In an effort to improve the prognosis of surgical procedures on the heart, physicians and researchers have attempted to use pumps to assist blood flow during surgery. However, such pumps only act as temporary assist devices during surgery, they cannot be used as a form of treatment for the cardiac condition.
An alternative, or at least a compliment, to coronary by-pass and other surgical procedures to improve blood flow in the heart is to induce tissues in the heart to form new blood vessels. In that regard, angiogenic compounds such as vascular endothelial growth factor (VEGF), have been used in an effort to facilitate the formation of new blood vessels. One approach to using VEGF to promote blood vessel formation in heart tissue has been to inject the protein directly into a patient's body. However, such attempts have been largely unsuccessful.
Recently, a gene-therapy approach was used to deliver VEGF by injection of retroviral vectors that targeted heart tissue and resulted in VEGF production (Losordo et al., 1998, Circulation 98:2800-2804). This in situ method improved blood flow and subjective symptoms in patients, suggesting that local delivery of a growth factor such as VEGF to promote angiogenesis in heart tissues may be of therapeutic value in the treatment of certain heart conditions. However, such gene therapy techniques utilizing retroviral vectors present certain inherent risks and safety concerns. In addition, gene therapy-type approaches present a number of unresolved, problematic technical hurdles such as low transfection levels for recipient cells, construct instability and long-term expression of the desired gene product from the transfected cells.